How the microbiome ages

I came across this interesting article currently in peer review (thus may have issues):

Human microbiome aging clocks based on deep learning and tandem of permutation feature importance and accumulated local effects

If the results are correct, then it may give great insight to age-related diseases caused by the microbiome changing. The claim that a healthy’s person’s age can be determined with 4 years from their microbiome (with 95% accuracy) is a surprise, but very likely true.

“Some microbes showed steadily increasing age prediction with increasing abundance (e.g. [Eubacterium] hallii); other microbes were on the opposite, inversely correlating with predicted age (e.g. Bacteroides vulgatus)… certain microbes that were previously identified as important by PFI showed little influence on predicted age (e.g. [Eubacterium] rectale) ”

Among the interesting findings are the following that decreases with age:

  • Bacteroides thetaiotaomicron
  • Bacteroides vulgatus
  • Bifidobacterium bifidum
  • Bifidobacterium longum
  • Odoribacter splanchnicus
  • Streptococcus salivarius

The following increase with age:

  • Lactobacillus reuteri
  • Lactococcus lactis
  • Propionibacterium freudenreichii

Bottom Line

Their AI model is not available on line (I wish it was and could accept ubiome data sets). It presents a significant step forward for determining what should be expected for an individual based on age. There are other factors that should also be included.

Addendum


Major faecal microbiota shifts in composition and diversity with age in a geographically restricted cohort of mothers and their children (2014)

Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study (2016)

Good probiotics for Histamine Issues

A reader wrote today me today on my Histamine post from July 2018

“Hi Ken, thank you for all the info you provide with this blog. In an older post, you recommended Lactobacillus Rhamnosus GG and E. Coli Nissle 1917 for reducing histamine. Does this advice still hold true? Are there any other strain worth trying? “

I will revisit the two probiotics he asked about (since more data is always coming in). See the link post for more information on Histamine in general.

Lactobacillus Rhamnosus

one billion viable microencapsulated bacteria Lactobacillus rhamnosus GG in combination with fructooligosaccharides to complex therapy of premature children results in regulation of cytokine balance with the tendency to reduction of an inflammatory process and has a preventive effect concerning allergopathy formation.

INVESTIGATION OF PROTECTIVE EFFECTS OF SYNBIOTICS ON ALLERGOPATHY FORMATION. 2018

Treatment with the probiotic mixture(four species of probiotics, Bifidobacterium lactis, Lactobacillus casei, Lactobacillus rhamnosus, and Lactobacillus plantarum) and sodium butyrate reduced ear thicknesses, the quantity of leaked Evans blue, and serum histamine values, while increasing serum IL-10 values.

Anti-Inflammatory Effects of a Mixture of Lactic Acid Bacteria and Sodium Butyrate in Atopic Dermatitis Murine Model. 2018

Escherichia Coli Nissle 1917 (Mutaflor)

We do not have such clarity for Mutaflor. We do find that it reduces allergies:

Other Strains

” Histamine derived from lactobacilli isolates is considered to be a potential immunomodulator able to interact with the host immune system….
 However, our findings indicated that the impact of lactobacilli histamine is strictly strain-dependent and concentration dependent.    ” [2018]

“These probiotic strains showed neither hemolytic activity nor mucin degradation activity, and they did not produce ammonia or biogenic amines (i.e., cadaverine, histamine or tyramine)

Safety Evaluations of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI. 2018

“Here, we investigated the effect of Lac-B, a mixture of freeze-dried Bifidobacterium infantis and Bifidobacterium longum, on the allergy-related histamine signaling. … Our findings indicate that oral administration of Lac-B showed significant anti-allergic effect through suppression of both H1R and HDC gene expression followed by decrease in H1R, HDC protein level, and histamine content. 

Suppression of histamine signaling by probiotic Lac-B: a possible mechanism of its anti-allergic effect. 2008
  • “Use of a probiotic mixture containing Bifidobacterium animalis subsp. lactis BB12 and Enterococcus faecium L3 in atopic children….
    significantly reduced the use of oral antihistamines, ” [2018]

Products Claiming…

There are some probiotic mixtures claiming not to produce histamines, for example: “ProBiota HistaminX contains only probiotic species that are considered “histamine-friendly” and excludes those known to produce histamine in the gut.* “.

Checking for responses from people who tried it

“hmm…first time I took bif inf I started with small amount , part of a capsule, and got bellyache from it ( therapist had told me nobody ever gets bellyache from it, can given safely to babies…well, lets say i know my belly better then he does) ” [Phoenix Rising]

Bottom Line

The strongest evidence is for Lactobacillus rhamnosus with caution suggested for other Lactobacillus.

Streptococcus faecium and Streptococcus faecalis produce or not produce histamine depending on strain [1990] “Forty-one (31.5%) of the S. faecium strains and 2 (1.9%) of the S. faecalis strains produced histamine. ” [1988]

“the histamine producing strain Streptococcus thermophilus PRI60” [2014]

  • So Streptococcus faecalis have a low risk of producing histamines.

Bifidobacterium (keep to the cited ones) appear promising (the ProBiota HistaminX has a lot of them in it).

There are a variety of sites, that gives lists of good and bad bacteria — unfortunately, they do not cite sources (or solid sources).

Florasan-D – alternatives

A reader wrote about this probiotic: ” with a special probiotic that i buy in Russia , i was having great results amazing “. He provided a link to it.

A research group at the First Moscow State Medical University has reported that they have identified a probiotic that eradicates eradicates small intestinal bacterial overgrowth (SIBO) in patients who also have irritable bowel syndrome (IBS).  The probiotic, available only in Russia, combinated four strains of bacteria and is named Florasan-D. Florasan-D includes a combination of Bifidobacterium bifidum,Bifidobacterium longum, Bifidobacterium infantis and Lactobacillus rhamnosus.


The findings revealed that both IBS-C and  IBS-D patients treated with the probiotic experienced statistically significant improvements in several measures (abdominal pain and stool frequency) after 28 days, compared with baseline.

Gut-Chek Blog

This did not cure SIBO/IBC-C/IBS-D. It improved it for some. He is likely one of the lucky ones. He is facing a problem because he is no longer able to buy it and asked for my help.

The research study is here (American Journal of Clinical Medicine Research, 2015 3 (2), pp 18-23.) And this chart may clarify “improves” and does not cure.

I was unable to find anything on the strains in this mixture nor their relative percentage. I found a Russian Reference that the dosage was 250 mg/day.

Replacement?

We are wishing the following:

  • Bifidobacterium bifidum,
  • Bifidobacterium longum,
  • Bifidobacterium infantis and 
  • Lactobacillus rhamnosus

CustomProbiotics

They have a 5 strain bifidobacteria containing the 3 above (with B. Lactis and B.Breve being the additional ones). They also sell pure Lactobacillus rhamnosus or use Culturelle (L. Rhamnosus GG).

They also have D-Lactate Free Probiotic Powder containing all of these, plus two more. IMHO — this would be my preferred substitution

  • L. Rhamnosus, Strain LR-32 -MATCH
  • L. Salivarius, Strain LS-33
  • B. Lactis, Strain BL-04
  • B. Bifidum, Strain Bb-06 – MATCH
  • B. Infantis, Strain Bi-26 – MATCH
  • B. Longum, Strain BL-05 – MATCH

Lifted Naturals Bifidus Mood Super Strains

This contains the same bifiobacteriums PLUS B. Breve and LGG.

Ingredients

L. rhamnosus (GG), B. longum, B. bifidum, B. lactis, B. breve, B. infantis

Bottom Line

In general, I do not recommend combinations probiotics because each species/strains has different impacts making the net effect fuzzy. Finding a reasonable replacement for the combination that helped this person is possible. My number 1 choice would be:

D-Lactate Free Probiotic Powder

Then Bifidus Mood Super Strains

Noise Sensitivity and the Gut

Another interesting article showed up from AI detecting atypical articles on PubMed. I strongly suspect that this applies to noise sensitive individuals (
Hyperacusis). There are no studies on Hyperacusis microbiome

Effects of chronic noise on glucose metabolism and gut microbiota-host inflammatory homeostasis in rats. [2016]

 Chronic noise exposure increased blood glucose and corticosterone levels for at least 14 days after cessation of noise. Stressed rats also exhibited elevated levels of glycogen and triglyceride in the liver and impaired hepatic insulin production via insulin-induced insulin receptor/insulin receptor substrate 1/glycogen synthase kinase 3β signalling, which persisted for 3-14 days after cessation of noise exposure. Chronic noise altered the percentage of Proteobacteria and Actinobacteria in the gut, increasing Roseburia but decreasing Faecalibacterium levels in the cecum relative to controls. Immunoglobulin A, interleukin 1β, and tumor necrosis factor α levels were also elevated in the intestine of these animals, corresponding to noise-induced abnormalities in glucose regulation and insulin sensitivity. These results suggest that lifelong environmental noise exposure could have cumulative effects on diabetes onset and development resulting from alterations in gut microbiota composition and intestinal inflammation.

Effects of chronic noise on glucose metabolism and gut microbiota-host inflammatory homeostasis in rats. [2016]

Human Studies

 IL-12 levels increased, whereas the NKT cell population decreased with increasing noise levels. The results further suggested that cortisol levels are more influenced by the subject’s sensitivity to noise than to the level of chronic road traffic noise. Therefore, noise appears to have the largest effect on IL-12 levels as well as the population and activity of NKT cells. In conclusion, our results suggest that low-level road traffic noise and sensitivity to noise can affect health by causing changes in the immune response through mechanisms other than increased cortisol.

Effects of self-reported sensitivity and road-traffic noise levels on the immune system. [2017]

Exposure to noise in work environment increases the incidence of tension and inappropriate behavior associated with aggression. Controlling noise through use of protective equipment might reduce the deleterious effects of noise on workers.

Effect of Chronic Noise Exposure on Aggressive Behavior of Automotive Industry Workers. [2018]

Note that hypertension(high blood pressure) is associated with these microbiome shifts

Bottom Line

I suspect there is a feedback cycle between the microbiome and
hyperacusis.

Looking at contributed samples that reported hyperacusis (some 73!), we see some significant patterns;

We do not know if the shifts caused the hyperacusis OR the hyperacusis caused the shifts OR there was a feedback cycle between the two,

How much vitamin D should you take for a healthy microbiome?

The last post, we found that research had found the vitamin D was the key component for a cascade that influenced B Vitamins, sleep and some digestive issues. This post will try to address the issue of vitamin D dosage.

On my old web site, I had done several posts on Vitamin D (from 2005-2006) – with links to PubMed articles.

In this post, I will jump to the bottom line fast (if you want more detail, see above).

Target Level

  • “The patients with optimal vitamin D status [25(OH)D ≥75 nmol/l]  ” [2016]
  • “Serum iPTH held a stable plateau level at 36 pg/ml as long as serum 25(OH)D values were higher than 78 nmol/l (31 ng/ml), but increased when the serum 25(OH)D value fell below this. ” [1997]
  • “Evidence is reviewed that shows that serum 25(OH)D3 concentrations of < 80 nmol/L are associated with reduced calcium absorption, osteoporosis, and increased fracture risk.” [2004]
  • In my posts from a decade ago, I created this chart using an image from an article from [2004]
Functional indices of vitamin D status and ramifications of vitamin D deficiency.

My suggested target level is 120 nmol/l. 50% above the level that issues start.

How much to take?

This is easy if you know your current level due to a chart from 2004,


Connie M Weaver and James C Fleet, Vitamin D requirements: current and future  
Am J Clin Nutr 2004;80(suppl):1735S–9S

Find the best match in the chart. I will take the high lighted one:

  • Actual reading: 66 nmol/l
  • Chart target: 80 nmol/l
  • Difference: 14 nmol/l
  • Amount to take: 1371 IU
  • So: 1371 IU/14 = 100 IU for each number below. Since our goal is 120 nmol/l, (120-66) * 100 = 5,400 IU/day

A reader indicated their level was 18 nmol/l. this becomes (120-18) * 100 = 12,000 IU/day.

Bottom Line

The numbers above are from the literature assuming no complicating factors such as those listed below. 

In these cases the dosages may need to be up to 10x more.

Any process resulting in malabsorption of intestinal fat may impair the absorption of vitamin D. In one study, absorption of tritium-labeled (3H)-vitamin D in normal subjects ranged from 62.4% to 91.3% of the initial oral dose (10). In patients with celiac disease, biliary obstruction absorption and chronic pancreatitis, absorption fell to 50%, < 28% and < 18% of the oral dose, respectively. In each case, impaired vitamin D absorption correlated with the degree of steatorrhea. Other conditions in which vitamin D absorption is impaired include liver failure (see below), cystic fibrosis, Crohn’s disease, and gastric bypass. Individuals taking bile acid-binding medications (such as colestyramine and colestipol for hypercholesterolemia) will also have impaired vitamin D absorption

Factors Influencing Vitamin D Status (2011)

The proper process is simple: Get your base line, do the computed amount above for 3 months, measure again. According to the literature you should be at the desired level by then. If you are 10% below, increase the dosage by 10%. This is the only way to estimate the degree of malabsorption.